Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians.

AIMS: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians. METHODS: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis. RESULTS: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 × 10(-17)) and individuals with extremes of genetic risk score (≥ 29.0 and ≤ 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 × 10(-4)), fat mass per cent (P = 2.4 × 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 × 10(-3) for both), as well as insulin resistance (P =0.02). CONCLUSIONS: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors.

Role of aneurysm projection in "A2" fork orientation for determining the side of surgical approach.

PURPOSE: To determine factors that help decide the side of approach for anterior communicating artery (AComA) aneurysms, based on a prospective study. METHODS: Between January 2004 and January 2006, 93 cases with AComA aneurysms were treated through pterional approach. They were classified as Type I, II (IIa, IIb), III and IV, based on the various projections and size of aneurysm. The principle for the choice of operative side was designed based on the type of aneurysm and the A2 fork orientation (the interrelations between the plane of bilateral A2, AComA, and mid-saggital plane). RESULTS: There were 55 aneurysms of Type I, 10 of Type IIa, 14 of Type IIb, 12 of Type III, and 2 of Type IV. In Types I and IIa, the side posteriorly placed to A2 was chosen for the approach. In Type IIb, the side of the dominant A1 was selected. In Type III, the side anteriorly placed to A2 was chosen. Type IV aneurysms were difficult to handle even if approached from the dominant A1. There were 11 cases treated from the side of non-dominant A1. The overall outcome in the treatment of AComA aneurysms were considered excellent in 90.8% of cases according to the Glasgow Outcome Scale, with complete occlusion of aneurysms and complete patency of parent or perforating arteries. CONCLUSIONS: Applying three-dimensional computed tomography and magnetic resonance angiography, we classified AComA aneurysms as four types and undertook surgical clipping from the chosen side of approach, according to the type of aneurysm and the A2 fork orientation. The selective side of approach on the basis of individual decision-making has led to favourable outcomes.

A classification of unruptured middle cerebral artery bifurcation aneurysms that can help in choice of clipping technique.

Middle cerebral artery (MCA) aneurysms comprise 20-25% of all intracranial aneurysms. The majority of middle cerebral artery aneurysms are treated by microsurgical clipping. Most of the classifications of aneurysms at present are based on size, location or pathology which are effective for the description but are less useful in preoperative planning and also in deciding on the technique or type of clip application. The aim of our study was to examine the morphological features of unruptured MCA bifurcation aneurysms which influence the techniques of clipping of these aneurysms and to attempt to subclassify unruptured middle cerebral artery aneurysms based on their preoperative 3D CTA and intraoperative characteristics so as to help in the intraoperative choice of technique and clip application, respectively. Preoperative 3D CT angiography and intraoperative images along with the record of technique and type of clips used for 141 unruptured MCA aneurysms operated at our center were studied retrospectively. Unruptured MCA bifurcation aneurysms could be subclassified into 5 types based on the similarities in their morphological features which influenced the techniques of clipping as recorded from their preoperative 3D CTA and intraoperative view. These types and the distinctive feature of each type are described. The various techniques of clipping are discussed based on these subgroups. The groups outlined make possible the establishment of a common technical approach to clipping within the groups. This classification, based on preoperative 3D CTA and intraoperative morphological features of the aneurysm and parent vessels, helps in the intraoperative choice of technique and type of clip application to tackle these lesions.